Should We Be Concerned About SARS-CoV-2 Reinfections?

This document is a part of a series of discussion notes addressing fundamental questions about the COVID-19 crisis and response strategies. These documents are based on the best scientific information available and may be updated as new information comes to light.

Written by Quique Bassat, Carlota Dobaño, Gonzalo Fanjul, Jose Muñoz, Antoni Plasència, Adelaida Sarukhan and Rafael Vilasanjuan (ISGlobal), the document addresses what we currently know about the frequency of reinfections or how they could affect the global vaccination strategy, among other key questions. 

From a scientific point of view, there are three fundamental questions about reinfection that we cannot answer with certainty on the basis of the information currently available:

• What is the frequency of reinfections?
• How serious is the second infection compared to the first one?
• To what extent do reinfections contribute to the spread of the virus?

The most reliable estimates suggest that one in ten people worldwide have already been infected by the SARS-CoV-2 coronavirus. In this context, the possibility that people could be reinfected with the virus casts a shadow over the strategy against COVID-19. Reports of second episodes of infection in people who had already been infected have recently started to emerge.

So far, cases of reinfection remain anecdotal. At least six cases have been documented in such disparate locations as Hong Kong, the United States, Belgium, Ecuador and India. Although four of these reports are still in the pre-print stage and the cases identified are the exception in a pool of more than 36 million confirmed infections worldwide, the reality is that thelack of data and the limitations of tracing systems may be obscuring other similar episodes.

What Do We Currently Know About the Immune Response to SARS-Cov-2?

1. Possibility of reinfection. Most experts agree that reinfections are to be expected, but are likely to be mild and with limited consequences, although serious cases associated with individual risk factors cannot be ruled out.
2. Post-infection immunity. As research advances, it is becoming clear that the immune response is highly heterogeneous among individuals. Some people do not produce antibodies, although all appear to generate SARS-CoV-2-reactive T cells. We still do not know what type and threshold of antibodies and T cells protect against infection and disease (correlates of protection). This is a fundamental limitation.
3. Duration of the immune response. The incidence of reinfection may increase 6-12 months after the first infection. Better monitoring of reinfections will therefore be critical in the next phase of the pandemic. The first generation of vaccines could delay a possible upsurge of reinfections. However, the same uncertainties surrounding natural immunity apply to vaccine-induced immunity: Will immunity last over time, or will people need to be revaccinated periodically?

How Can We Answer the Questions Surrounding Reinfection?

The only way to answer these questions is to actively monitor cases over time to determine the type, magnitude and duration of the immune responses and their impact on protection against reinfection.

Until more information is available and as long as the risk of infection remains significant, people who have already had the disease must keep following the same preventive measures, including mask-wearing and hand hygiene.

Global Vaccination Strategy

It is important to note that we do not yet know whether the immunity conferred by the vaccines currently in development will be of the same type and duration as natural immunity. Vaccines are expected to induce stronger, longer-lasting and more homogeneous immunity than the immunity conferred by natural infection, particularly in cases with mild or no symptoms, but this has yet to be proven. (Several of the more advanced candidate vaccines use technology that has never before been used in humans.)

In any case, reinfection does not mean that vaccines are not effective. What it could mean is that much of the population might require one or more booster doses after a certain period of time.

It is also possible that vaccines will only reduce symptoms rather than prevent infection. If this is the case, vaccinated people would become asymptomatic carriers of the virus and could therefore infect members of vulnerable groups.

Conclusions

Given the information currently available, include the following:

• At present, reinfections are not a cause for alarm. Reinfections are also seen in many other respiratory viruses.
• We do not yet know how frequently reinfections occur. Very few cases have been documented so far.
• We do not yet understand the consequences of reinfection at the individual level (severity of symptoms after the second infection) or at the population level (ability to spread the virus). This is why it is important for people who have already had the infection to keep observing the same hygiene and prevention measures as the rest of the population.
• More information is needed on the type and duration of natural and vaccine-induced immunity.
• If reinfections are marginal and do not exacerbate the disease, people with antibodies need not be included in the first vaccination campaigns.
• If reinfections are frequent, booster doses may need to be administered regularly or after a certain period of time.